CLINICAL UPDATE
RETINA
Treat-and-Extend Strategy:
Is There a Consensus?
I
James C. Folk, MD
n an ideal world, every patient who
is undergoing intravitreal treatment
for neovascular age-related macular
degeneration (AMD) would return
faithfully, 12 times a year, for a lengthy
visit that includes a clinical examination, retinal imaging, and, possibly, an
intravitreal injection of an anti-VEGF
drug. In the real world, however, patients frequently have trouble meeting
this monthly schedule—and that places
their vision at risk.
“This comes up every day in my
practice,” said K. Bailey Freund, MD,
in private practice in New York City.
“Some of these patients are over 100
years old, and just to get them into the
office can be a difficult ordeal for themselves and their family members.”
One solution being adopted by
retinal physicians is “treat and extend,” a
dosing strategy that can enable patients
with wet AMD to go as long as 12 weeks
between office visits and injections.
Gaining Popularity
Despite limited evidence, positive clinical experiences with the treat-and-extend approach have fueled the spread of
the protocol in retinal practices around
the world, Dr. Freund noted.
A 2015 survey of retinal subspecialists found that 66.7% of the 586 U.S.
respondents preferred a treat-andextend regimen for their wet AMD
patients. Internationally, about a third
of the retinal physicians who responded
in Europe, Asia, and Latin America ex-
pressed a preference for this approach
to wet AMD therapy.1
An incremental approach. The
specifics vary among practitioners, but
in general terms, the regimen follows
this course, according to Dr. Freund:
The patient’s retina is first cleared of
macular fluid and retinal hemorrhages
with a series of monthly injections of
the chosen drug. Then the physician
begins extending the interval between
treatments, 2 weeks at a time, as long as
the retina remains dry and stable.
Who benefits? Treat and extend
“applies mainly to neovascular AMD.
You can also use it for treating patients
with diabetic macular edema or retinal
vein occlusions,” said Dr. Freund, who
led a group that coined the term “treat
and extend” in a 2010 paper.2
Coming to a Consensus
More recently, Dr. Freund was part of
an international panel of retinal physicians that developed an algorithm for
using treat and extend against retinal
diseases, based on their clinical experience and information from published
studies.3 (For the algorithm, see this
article at www.eyenet.org.)
A key tool: OCT. The panel recommended monitoring for subretinal and
intraretinal fluid with optical coherence tomography (OCT), in order to
assure the retina’s readiness for a longer
treatment interval. In most cases, the
experts deemed fluorescein angiography unnecessary as therapy proceeds.
BY LINDA ROACH, CONTRIBUTING WRITER, INTERVIEWING PRAVIN U.
DUGEL, MD, K. BAILEY FREUND, MD, AND ADRIENNE WILLIAMS SCOTT, MD
TREAT AND EXTEND. Proponents of
this regimen say that it can reduce the
treatment burden for patients under­
going injections.
Timing the extensions. “Let’s say
that after 3 monthly injections, the
patient achieved what you determine
is the maximum response, based on
OCT,” Dr. Freund said. “Then you
might have the patient come back in 6
weeks; and if they’re still stable, then
you would inject and have them return
in 7 or 8 weeks. So you could be seeing
patients half as often, but they [would]
get a treatment every time they come.”
When to reconsider. The algorithm
recommends a maximum interval between injections of 12 weeks and notes
that the injection interval sometimes
must be shortened, Dr. Freund said. “If
there are minor changes between visits,
such as a small increase in fluid, then
all you do is go back to the interval that
had kept them completely dry. Only in
the situation of a major event, such as
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a large hemorrhage, would you revert
back to monthly treatment.”
Different from PRN. Under treat
and extend, the patient receives an
anti-VEGF injection at every visit. That
is in contrast to OCT-guided pro re
nata (PRN), which has been shown to
be effective in clinical trials. With PRN,
OCT imaging and a clinical exam continue to be performed monthly. However, the patient receives an injection
only if the OCT shows a recurrence of
fluid or hemorrhage.
Practical Benefits
“I use treat and extend quite frequently,” said Adrienne Williams Scott,
MD, at Johns Hopkins University in
Baltimore. “I find it to be a practical
regimen in which you can maintain the
vision gains from anti-VEGF therapy
yet minimize the injections and the
burden on patients.”
Pravin U. Dugel, MD, agreed. “In
every survey that I know of, treat and
extend is the regimen that is most
used by retina specialists.” Dr. Dugel
is at Retinal Consultants of Arizona in
Phoenix and the University of Southern
California’s Eye Institute in Los Angeles. In addition to lessening the burden
on patients, treat-and-extend regimens
help clinicians cope with the unknowns
of retinal neovascularization, Dr. Dugel
said. “There’s a great deal of variability
between patients, and we have no way
to predict who will respond and how.
So treat and extend seems to be logical.”
Parsing the Evidence
Literature review. The consensus panel
on which Dr. Freund served conducted a literature review and found 11
published studies reporting positive
outcomes with treat and extend in eyes
with neovascular AMD.3 Most of the
studies were small or retrospective, and
only one—the LUCAS trial—met Level
1 criteria for demonstrating efficacy.4
LUCAS results. The LUCAS researchers found that treat and extend
with bevacizumab or ranibizumab gave
wet AMD patients mean increases in
best-corrected visual acuity (VA) of 7.9
and 8.2 letters, respectively, after 1 year
of treatment.4 This was comparable to
the VA gains in the CATT study, which
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2016
employed monthly injections of these
drugs; CATT gains were 8.0 and 8.5
letters, respectively, at 1 year.4 (For a
second report of LUCAS results, see
“Treat and Extend at 2 Years.”)
A Practical Compromise?
Dr. Scott said that she views treat and
extend as a therapeutic option for
patients who can’t—or won’t—comply
with a monthly dosing regimen. “Treat
and extend is really more of a compromise,” she said. “Because when you look
at Level 1 evidence from large pivotal
clinical trials, the best results have come
with monthly treatment. The patients
who are injected monthly tend to do
the best in terms of less vision lost,
more vision gained, and drier OCTs.”
Dr. Dugel agreed. “We know in real
life that none of us are getting visual
outcomes as good as the published
trials, because the treatment burden
would be far too arduous.” He said he
moves patients who have had trouble
coming in for monthly visits to a treatand-extend approach. “I tell them that I
think the results we get will probably be
as good—or almost as good—as they
would be with monthly surveillance.
But that is based on my clinical experience, not on Level 1 data.”
While Dr. Freund agrees that data
supporting treat and extend are not as
robust as those for monthly treatment,
he emphasized the chronic nature of
neovascular AMD. “The reality is that
some patients will require treatment for
10 years or longer. This fact necessitates
a viable management strategy, such as
treat and extend, that can be maintained for this duration.” l
1 American Society of Retina Specialists. 2015
Global Trends in Retina Survey Results. Available
at https://www.asrs.org/international/globaltrends-in-retina. Accessed Oct. 23, 2015.
2 Engelbert M et al. Retina. 2010;30(9):13681375.
3 Freund KB et al. Retina. 2015;35(8):1489-1506.
4 Berg K et al. Ophthalmology. 2015;122(1):146152.
Dr. Dugel is managing partner at Retinal Con­
sultants of Arizona and the Retinal Research
Institute in Phoenix and clinical professor of
ophthalmology at the University of Southern
California’s USC Eye Institute and Keck School of
Medicine in Los Angeles. Relevant financial disclosures: Abbott Medical Optics: C; Acucela: C; Alcon:
C; Alimera Sciences: C,O; Allergan: C; Digisight: O;
Genentech: C; Novartis: C; Ophthotech: C,O; Ora:
C; Regeneron: C; ThromboGenics: C.
Dr. Freund practices at Vitreous-Retina-Macula
Consultants of New York and is clinical professor of ophthalmology at New York University
Med­ical Center. Relevant financial disclosures:
Bayer Healthcare: C; Genentech: C; Heidelberg
Engineering: C; Ohr: C; Optos: C; Optovue: C;
ThromboGenics: C.
Dr. Scott is assistant professor of ophthalmology
at Johns Hopkins University in Baltimore. Relevant financial disclosures: ThromboGenics: S.
See the disclosure key, page 8.
MORE ONLINE. For the full
treatment algorithm and
additional comments, view this article
online at www.eyenet.org.
Treat and Extend at 2 Years
The LUCAS researchers compared the efficacy and safety of bevacizumab
and ranibizumab for neovascular AMD when the drugs are delivered via a
strict treat-and-extend protocol. They found equivalent outcomes between
the 2 agents with regard to VA and central retinal thickness (CRT).1 A total of 339 patients were available for analysis. At the 2-year mark,
bevacizumab was equivalent to ranibizumab, with 7.4 and 6.6 letters gained,
respectively. Mean CRT decreased by –113 µm in those who received bevacizumab and by –122 µm in those who received ranibizumab. All told, those in
the bevacizumab group received 18.2 injections, versus 16.0 injections in the
ranibizumab group. When serious adverse events were evaluated, no significant differences emerged between the treatment groups.
1 Berg K et al. Ophthalmology. Published online Oct. 15, 2015. doi: 10.1016/j.ophtha.
2015.09.018.